Dr. Julie Kauer received her Ph.D. from Yale University in 1986, and then carried out postdoctoral work with Dr. Roger Nicoll (UCSF) and Dr. Richard Tsien (Stanford University). Since beginning her own laboratory, first at Duke University School of Medicine and now as Professor of Medical Science at Brown University, she has become a leader in the field of synaptic transmission and plasticity. Dr. Kauer has organized and chaired the Gordon Research Conference on Synaptic Transmission in 2006, and she was a member of the NINDS Board of Scientific Counselors from 2008-2013. She recently was recognized for her contributions to synaptic neurobiology by being named Fellow of the American Association for the Advancement of Science. The Kauer lab has made key contributions to our understanding of synaptic plasticity at inhibitory synapses in the brain circuitry underlying reward and addiction, and recently has identified for the first time synaptic plasticity at glycinergic synapses, a type of inhibitory synapse prevalent in the spinal cord.
|Pradier B, Shin HB, Kim DS, St Laurent R, Lipscombe D, Kauer JA. "Long-Term Depression Induced by Optogenetically Driven Nociceptive Inputs to Trigeminal Nucleus Caudalis or Headache Triggers." Journal of Neuroscience, vol. 38, no. 34, 2018, pp. 7529-7540.|
|Pradier B, Lanning K, Taljan KT, Feuille CJ, Nagy MA, Kauer JA. "Persistent but Labile Synaptic Plasticity at Excitatory Synapses." Journal of Neuroscience, vol. 38, no. 25, 2018, pp. 5750-5758.|
|Polter AM, Barcomb K, Tsuda AC, Kauer, JA. "Synaptic function and plasticity of inhibitory inputs onto VTA dopamine neurons." Eur. J. Neurosci., vol. 47, 2018, pp. 1208-1218.|
|Polter AM, Barcomb K, Chen RW, Dingess PM, Graziane NM, Brown TE, Kauer JA. "Constitutive activation of kappa opioid receptors at ventral tegmental area inhibitory synapses following acute stress." eLife, vol. 6, 2017.|
|Dingle YT, Boutin ME, Chirila AM, Livi LL, Labriola NR, Jakubek LM, Morgan JR, Darling EM, Kauer JA, Hoffman-Kim D. "Three-Dimensional Neural Spheroid Culture: An In Vitro Model for Cortical Studies." Tissue engineering. Part C, Methods, vol. 21, no. 12, 2015, pp. 1274-83.|
|Chirila AM, Brown TE, Bishop RA, Bellono NW, Pucci FG, Kauer JA. "Long-term potentiation of glycinergic synapses triggered by interleukin 1β." Proceedings of the National Academy of Sciences, vol. 111, no. 22, 2014, pp. 8263-8.|
|Polter AM, Bishop RA, Briand LA, Graziane NM, Pierce RC, Kauer JA. "Poststress block of kappa opioid receptors rescues long-term potentiation of inhibitory synapses and prevents reinstatement of cocaine seeking." Biological Psychiatry, vol. 76, no. 10, 2014, pp. 785-93.|
|Polter AM, Kauer JA. "Stress and VTA synapses: implications for addiction and depression." European Journal of Neuroscience, vol. 39, no. 7, 2014, pp. 1179-88.|
|Kauer JA, Polter AM. "Yin and Yang: unsilencing synapses to control cocaine seeking." Neuron, vol. 83, no. 6, 2014, pp. 1234-6.|
|Ouyang Q, Lizarraga SB, Schmidt M, Yang U, Gong J, Ellisor D, Kauer JA, Morrow EM. "Christianson syndrome protein NHE6 modulates TrkB endosomal signaling required for neuronal circuit development." Neuron, vol. 80, no. 1, 2013, pp. 97-112.|
|Graziane NM, Polter AM, Briand LA, Pierce RC, Kauer JA. "Kappa opioid receptors regulate stress-induced cocaine seeking and synaptic plasticity." Neuron, vol. 77, no. 5, 2013, pp. 942-54.|
|Brown TE, Chirila AM, Schrank BR, Kauer JA. "Loss of interneuron LTD and attenuated pyramidal cell LTP in Trpv1 and Trpv3 KO mice." Hippocampus, vol. 23, no. 8, 2013, pp. 662-71.|
|Edwards JG, Gibson HE, Jensen T, Nugent F, Walther C, Blickenstaff J, Kauer JA. "A novel non-CB1/TRPV1 endocannabinoid-mediated mechanism depresses excitatory synapses on hippocampal CA1 interneurons." Hippocampus, vol. 22, no. 2, 2012, pp. 209-21.|
|Sumioka A, Brown TE, Kato AS, Bredt DS, Kauer JA, Tomita S. "PDZ binding of TARPγ-8 controls synaptic transmission but not synaptic plasticity." Nature Neuroscience, vol. 14, no. 11, 2011, pp. 1410-2.|
|Niehaus JL, Murali M, Kauer JA. "Drugs of abuse and stress impair LTP at inhibitory synapses in the ventral tegmental area." European Journal of Neuroscience, vol. 32, no. 1, 2010, pp. 108-17.|
|Kauer JA, Gibson HE. "Hot flash: TRPV channels in the brain." Trends in Neurosciences, vol. 32, no. 4, 2009, pp. 215-24.|
|Nugent FS, Niehaus JL, Kauer JA. "PKG and PKA signaling in LTP at GABAergic synapses." Neuropsychopharmacology, vol. 34, no. 7, 2009, pp. 1829-42.|
|Niehaus JL, Cruz-Bermudez ND, Kauer JA. "Plasticity of addiction: a mesolimbic dopamine short-circuit?." The American Journal on Addictions, vol. 18, no. 4, 2009, pp. 259-71.|
|McBain CJ, Kauer JA. "Presynaptic plasticity: targeted control of inhibitory networks." Current opinion in neurobiology, vol. 19, no. 3, 2009, pp. 254-62.|
|Nugent FS, Hwong AR, Udaka Y, Kauer JA. "High-frequency afferent stimulation induces long-term potentiation of field potentials in the ventral tegmental area." Neuropsychopharmacology, vol. 33, no. 7, 2008, pp. 1704-12.|
|Nugent FS, Kauer JA. "LTP of GABAergic synapses in the ventral tegmental area and beyond." The Journal of Physiology, vol. 586, no. 6, 2008, pp. 1487-93.|
|Wang Z, Edwards JG, Riley N, Provance DW Jr, Karcher R, Li XD, Davison IG, Ikebe M, Mercer JA, Kauer JA, Ehlers MD. "Myosin Vb mobilizes recycling endosomes and AMPA receptors for postsynaptic plasticity." Cell, vol. 135, no. 3, 2008, pp. 535-48.|
|Gibson HE, Edwards JG, Page RS, Van Hook MJ, Kauer JA. "TRPV1 channels mediate long-term depression at synapses on hippocampal interneurons." Neuron, vol. 57, no. 5, 2008, pp. 746-59.|
|Kauer, Julie A. "TRPV1: hot new channels in the brain." Future Neurology, vol. 3, no. 5, 2008, pp. 507-510.|
|Mair RD, Kauer JA. "Amphetamine depresses excitatory synaptic transmission at prefrontal cortical layer V synapses." Neuropharmacology, vol. 52, no. 1, 2007, pp. 193-9.|
|Nugent FS, Penick EC, Kauer JA. "Opioids block long-term potentiation of inhibitory synapses." J. Geophys. Res., vol. 446, no. 7139, 2007, pp. 1086-90.|
|Kauer JA, Malenka RC. "Synaptic plasticity and addiction." Nature Reviews Neuroscience, vol. 8, no. 11, 2007, pp. 844-58.|
|Kauer JA, Malenka RC. "LTP: AMPA receptors trading places." Nature Neuroscience, vol. 9, no. 5, 2006, pp. 593-4.|
|Kauer JA. "Inhibitory synapses turn exciting." Nature Neuroscience, vol. 8, no. 3, 2005, pp. 257-8.|
|Kauer JA. "Neuroscience: a home for the nicotine habit." J. Geophys. Res., vol. 436, no. 7047, 2005, pp. 31-2.|
|Kauer JA. "Learning mechanisms in addiction: synaptic plasticity in the ventral tegmental area as a result of exposure to drugs of abuse." Annual review of physiology, vol. 66, 2004, pp. 447-75.|
|Faleiro LJ, Jones S, Kauer JA. "Rapid synaptic plasticity of glutamatergic synapses on dopamine neurons in the ventral tegmental area in response to acute amphetamine injection." Neuropsychopharmacology, vol. 29, no. 12, 2004, pp. 2115-25.|
|Park M, Penick EC, Edwards JG, Kauer JA, Ehlers MD. "Recycling endosomes supply AMPA receptors for LTP." Science, vol. 305, no. 5692, 2004, pp. 1972-5.|
|Li Y, Kauer JA. "Repeated exposure to amphetamine disrupts dopaminergic modulation of excitatory synaptic plasticity and neurotransmission in nucleus accumbens." Synapse (New York, N.Y.), vol. 51, no. 1, 2004, pp. 1-10.|
|Kauer JA. "Addictive drugs and stress trigger a common change at VTA synapses." Neuron, vol. 37, no. 4, 2003, pp. 549-50.|
|Faleiro LJ, Jones S, Kauer JA. "Rapid AMPAR/NMDAR response to amphetamine: a detectable increase in AMPAR/NMDAR ratios in the ventral tegmental area is detectable after amphetamine injection." Annals of the New York Academy of Sciences, vol. 1003, 2003, pp. 391-4.|
|Gutlerner JL, Penick EC, Snyder EM, Kauer JA. "Novel protein kinase A-dependent long-term depression of excitatory synapses." Neuron, vol. 36, no. 5, 2002, pp. 921-31.|
|Jones S, Kornblum JL, Kauer JA. "Amphetamine blocks long-term synaptic depression in the ventral tegmental area." Journal of Neuroscience, vol. 20, no. 15, 2000, pp. 5575-80.|
|Bliss T, Errington M, Fransen E, Godfraind JM, Kauer JA, Kooy RF, Maness PF, Furley AJ. "Long-term potentiation in mice lacking the neural cell adhesion molecule L1." Current Biology, vol. 10, no. 24, 2000, pp. 1607-10.|
|Jones S, Kauer JA. "Amphetamine depresses excitatory synaptic transmission via serotonin receptors in the ventral tegmental area." Journal of Neuroscience, vol. 19, no. 22, 1999, pp. 9780-7.|
|Kauer JA. "Blockade of hippocampal long-term potentiation by sustained tetanic stimulation near the recording site." Journal of Neurophysiology, vol. 81, no. 2, 1999, pp. 940-4.|
|Kandler K, Katz LC, Kauer JA. "Focal photolysis of caged glutamate produces long-term depression of hippocampal glutamate receptors." Nature Neuroscience, vol. 1, no. 2, 1998, pp. 119-23.|
|McMahon LL, Williams JH, Kauer JA. "Functionally distinct groups of interneurons identified during rhythmic carbachol oscillations in hippocampus in vitro." Journal of Neuroscience, vol. 18, no. 15, 1998, pp. 5640-51.|
|Tecott LH, Logue SF, Wehner JM, Kauer JA. "Perturbed dentate gyrus function in serotonin 5-HT2C receptor mutant mice." Proceedings of the National Academy of Sciences, vol. 95, no. 25, 1998, pp. 15026-31.|
|Kauer JA, McMahon LL. "Depressing transmission in GABAergic hippocampal neurons." Molecular Psychiatry, vol. 2, no. 6, 1997, pp. 434-6.|
|McMahon LL, Kauer JA. "Hippocampal interneurons are excited via serotonin-gated ion channels." Journal of Neurophysiology, vol. 78, no. 5, 1997, pp. 2493-502.|
|McMahon LL, Kauer JA. "Hippocampal interneurons express a novel form of synaptic plasticity." Neuron, vol. 18, no. 2, 1997, pp. 295-305.|
|Williams JH, Kauer JA. "Properties of carbachol-induced oscillatory activity in rat hippocampus." Journal of Neurophysiology, vol. 78, no. 5, 1997, pp. 2631-40.|
|Covey E, Kauer JA, Casseday JH. "Whole-cell patch-clamp recording reveals subthreshold sound-evoked postsynaptic currents in the inferior colliculus of awake bats." Journal of Neuroscience, vol. 16, no. 9, 1996, pp. 3009-18.|
|McBain CJ, DiChiara TJ, Kauer JA. "Activation of metabotropic glutamate receptors differentially affects two classes of hippocampal interneurons and potentiates excitatory synaptic transmission." Journal of Neuroscience, vol. 14, no. 7, 1994, pp. 4433-45.|
|Desai MA, McBain CJ, Kauer JA, Conn PJ. "Metabotropic glutamate receptor-induced disinhibition is mediated by reduced transmission at excitatory synapses onto interneurons and inhibitory synapses onto pyramidal cells." Neuroscience Letters, vol. 181, no. 1-2, 1994, pp. 78-82.|
|Nicoll RA, Malenka RC, Kauer JA. "Functional comparison of neurotransmitter receptor subtypes in mammalian central nervous system." Physiological reviews, vol. 70, no. 2, 1990, pp. 513-65.|
|Kauer JA, Malenka RC, Perkel DJ, Nicoll RA. "Postsynaptic mechanisms involved in long-term potentiation." Systems Biology of RNA Binding Proteins, vol. 268, 1990, pp. 291-9.|
|Malenka RC, Kauer JA, Perkel DJ, Mauk MD, Kelly PT, Nicoll RA, Waxham MN. "An essential role for postsynaptic calmodulin and protein kinase activity in long-term potentiation." J. Geophys. Res., vol. 340, no. 6234, 1989, pp. 554-7.|
|Malenka RC, Kauer JA, Perkel DJ, Nicoll RA. "The impact of postsynaptic calcium on synaptic transmission--its role in long-term potentiation." Trends in Neurosciences, vol. 12, no. 11, 1989, pp. 444-50.|
|Nicoll RA, Malenka RC, Kauer JA. "The role of calcium in long-term potentiation." Annals of the New York Academy of Sciences, vol. 568, 1989, pp. 166-70.|
|Kauer JA, Malenka RC, Nicoll RA. "A persistent postsynaptic modification mediates long-term potentiation in the hippocampus." Neuron, vol. 1, no. 10, 1988, pp. 911-7.|
|Kauer JA, Malenka RC, Nicoll RA. "NMDA application potentiates synaptic transmission in the hippocampus." J. Geophys. Res., vol. 334, no. 6179, 1988, pp. 250-2.|
|Malenka RC, Kauer JA, Zucker RS, Nicoll RA. "Postsynaptic calcium is sufficient for potentiation of hippocampal synaptic transmission." Science, vol. 242, no. 4875, 1988, pp. 81-4.|
|Nicoll RA, Kauer JA, Malenka RC. "The current excitement in long-term potentiation." Neuron, vol. 1, no. 2, 1988, pp. 97-103.|
|Kauer JA, Fisher TE, Kaczmarek LK. "Alpha bag cell peptide directly modulates the excitability of the neurons that release it." Journal of Neuroscience, vol. 7, no. 11, 1987, pp. 3623-32.|
|Kauer JA, Kaczmarek LK. "Peptidergic neurons of Aplysia lose their response to cyclic adenosine 3':5'-monophosphate during a prolonged refractory period." Journal of Neuroscience, vol. 5, no. 5, 1985, pp. 1339-45.|
|Bekoff A, Kauer JA. "Neural control of hatching: fate of the pattern generator for the leg movements of hatching in post-hatching chicks." Journal of Neuroscience, vol. 4, no. 11, 1984, pp. 2659-66.|
My major research focus for many years has been on synaptic plasticity, the strengthening or weakening of synaptic connections between neurons. Synaptic plasticity is a basic property of excitatory synapses in the central nervous system and is used in distinct brain regions for neuroadapations to various environmental stimuli. My lab's work has recnetly focused in two regions of the central nervous system 1) the midbrain ventral tegmental area (VTA), where we have been testing the hypothesis that synaptic plasticity is an early change that occurs during stress and is essential for addiction to drugs of abuse, and 2) the dorsal horn of the spinal cord, where synaptic plasticity contributes to the development of persistent pain. My lab uses electrophysiological recordings from neurons in acutely prepared slices, as well as optogenetic activation of specific neurons to identify their roles in circuit function. We have also utilized viral transfection, transgenic mice, and other tools to manipulate the protein environment in neurons to probe the roles of particular molecules in synaptic function.
My lab was one of the first to examine the relationship between synaptic plasticity and drugs of abuse. We and others have found that after even a single exposure to a drug of abuse in vivo, synapses in the VTA are potentiated. Amphetamine produces this potentiation within two hours of administration, consistent with an LTP-like mechanism. We have also demonstrated that a form of LTD at the same synapses is entirely blocked by brief exposure in vitro to low doses of amphetamine. We believe that the block of LTD by psychostimulant drugs may promote LTP of the same synapses and contribute to the development of addiction. We currently have two major directions in the VTA. First, we have discovered an entirely novel form of plasticity at VTA synapses. Little has previously been known about plasticity of inhibitory GABAergic synapses, and indeed many inhibitory synapses do not exhibit plasticity like their excitatory neighbors. We now find that inhibitory GABAergic VTA synapses express robust LTP mediated by an entirely novel intracellular signaling cascade. This LTPGABA is entirely blocked by morphine, suggesting a novel site of action for this drug in the reward circuit. Our recent work demonstrated that not only morphine but also other abused drugs and a brief stressor block LTPGABA and potentiate excitatory synapses. We know that stress can precipitate drug-seeking in animals that have undergone drug withdrawal, suggesting the idea that when LTPGABA is blocked (by stress), an individual may be more likely to relapse to drug use. We have found that stress-induced relapse to drug seeking correlates with the block of LTPGABA, and that a kappa opioid receptor antagonist rescues both LTPGABA and prevents stress-induced drug seeking in a rodent model of relapse.
Our secondarea of research involves characterizing synaptic plasticity at synapses between afferents carrying pain information and neurons in slices of spinal cord. We are examining different dorsal horn neurons to see which cells are involved, and we will also test synaptic function in slices in models of neuropathic pain. We have identified a novel form of synaptic plasticity at synapses in the dorsal horn at glycinergic receptors. Although glycine is one of the three major neurotransmitter systems in the central nervous system, very little is known about glycinegric synapses. We find that the proinflammatory cytokine, interleukin-1beta, rapidly causes potentiation of glycinergic synapses on specific neurons in the dorsal horn pain circuit. Intriguingly, the same potentiation occurs rapidly following inflammation of the paw. We are continuing to characterize this novel form of plasticity and its relationship to pain. We have also begun to use optogenetic stimulation in tissue slices to understand the circuits activated selectively by nociceptors.
Overall, our work in synaptic plasticity demonstrates that multiple signaling pathways are utilized at various CNS synapses to bring about changes in synaptic strength. Furthermore, our work in the reward system and dorsal horn emphasizes the idea that changes in synaptic strength contribute to neuroadaptations of many brain systems beyond those used to store memory per se. The interactions of drugs of abuse and of pain fibers with LTP and LTD mechanisms illustrate this idea: distinct environmental inputs may modify or perturb existing CNS systems to bring about long-lasting behavioral changes. My work thus is relevant both at the basic level, describing the building blocks of the nervous system, and at the translational level, suggesting targets for therapeutics that may enhance memory or combat addiction or chronic pain.
Brown University Seed Fund Award Kauer/Lipscombe (co-PIs) 03/15/2012 06/30/2013
"Molecular and Cellular Mechanisms Underlying the Transition from Acute to Chronic Pain"
NIH/NIDA RO1 Kauer (PI) 12/01/11 - 11/30/2016
"Inhibitory synaptic transmission, stress and drugs of abuse"
NIH/NINDS RO1NS088453 (Kauer, PI) 07/01/2014-06/30/2019
“Glycine receptor synaptic plasticity”
Polter, A.M., Bishop, R.A., Briand, L.A., Graziane, N.M., Pierce, R. C., and Kauer, J.A. Post-stress block of kappa opioid receptors rescues LTPGABA and prevents reinstatement of cocaine seeking. Biol. Psychiatry, in press.
Chirila, A.M., Brown, T.E., Bishop, R.A., Bellono, N.W., Pucci, F.G. and Kauer, J.A. (2014) Long-term potentiation of glycinergic synapses triggered by interleukin 1b. Proc. Natl. Acad. Sci. 111(22):8263-8. PMC4050559.
Ouyang, Q., Lizarraga, S.B., Schmidt, M., Yang, U., Gong, J., Ellisor, D., Kauer, J.A., and Morrow, E.M. (2013) Christianson syndrome protein NHE6 modulates TrkB endosomal signaling required for neuronal circuit development. Neuron 80: 97-112. PMC3830955.
Graziane, N.M., Polter, A.M., Briand, L.A., Pierce, R.C. and Kauer, J.A. (2013) Kappa opioid receptors regulate stress-induced cocaine-seeking and synaptic plasticity. Neuron 77: 942-954. PMC450723
Sumioka, A., Brown, T.E., Kauer, J.A. and Tomita, S. (2011) PDZ binding of TARP-8 controls synaptic transmission, but not synaptic plasticity. Nature Neurosci 14: 1410-12. PMC3206644
Niehaus, J.L., Murali, M. and Kauer, J.A. (2010) Drugs of abuse and stress impair LTP at inhibitory synapses in the ventral tegmental area. Eur J Neurosci 32: 108-117. PMC2908505
Wang Z., Edwards J.G., Riley N., Provance, D.W. Jr., Karcher R., Li X.-D., Davison I.G., Ikebe M., Mercer J.A., Kauer J.A., and Ehlers M.D. (2008) Myosin Vb mobilizes recycling endosomes and AMPA receptors for postsynaptic plasticity. Cell: 135: 535-548. PMC2585749
Gibson, H.E., Edwards, J.G., Page, R. S., Van Hook, M.J. and Kauer J.A. (2008) TRPV1 channels mediate long-term depression at synapses on hippocampal interneurons. Neuron 57: 746-759. PMC2698707
Kauer, J.A. and Malenka, R.C. (2007) Synaptic plasticity and addiction. Nature Rev Neurosci 8: 844-858.
Nugent, F.S., Penick, E.C., and Kauer, J.A. (2007) Opioids block long-term potentiation of GABAergic synapses. Nature 446:1086-90.
Scholar in Residence, University of Pennsylvania Systems and Integrative Behavior, 4/01
Vice Chair, Gordon Research Conference "Synaptic Transmission", 8/04
Chair, Gordon Research Conference "Synaptic Transmission", 7/06
Special Lecturer, Society for Neuroscience meeting 11/09
Invited Adrian Seminar in Neuroscience, Cambridge University, Cambridge UK, 5/09
Elected Fellow, American Association for the Advancement of Science, 2012
|Connors, Barry||L. Herbert Ballou University Professor of Neuroscience|
|Lipscombe, Diane||Thomas J. Watson, Sr. Professor of Science, Professor of Neuroscience, Reliance Dhirubhai Ambani Director of the Robert J. and Nancy D. Carney Institute for Brain Science|
|Moore, Christopher||Associate Director of the Carney Institute of Brain Science, Professor of Neuroscience|
|Saab, Carl||Professor of Neurosurgery (Research), Professor of Neuroscience (Research)|
Woods Hole Neurobiology course instructor, 1991, 1993
Woods Hole Neurobiology course lecturer, 1994-2002
Lecturer, Biotechnology for Business course, Duke University, 1993-2004
NIH Internal Review Group MDCN-5, 2000-2004
Associate Editor, Journal of Neuroscience, 2001-2006
Associate Editor, Journal of Neurophysiology, 2002-present
Society for Neuroscience Jacob P. Waletzky Memorial Award Committee, 2003
Society for Neuroscience Program Committee, 2003-2007
Editorial Board, Physiology, 2006-2012
NINDS Board of Scientific Counselors, 2008- 2013
Editorial Board, Physiological Reviews, 2010- present
AAAS, 2011- present
Ad hoc reviewer: Alzheimer's Association, Ireland Health Review Board, Wellcome Trust, Grass Fellowships, MRC fellowships (UK), NIDA Program Project (2005), Research Grants Council Hong Kong, MDCN-C Drug Development panel (2005), NIEHS review panel (2008), NICHD intramural review panel (2008).
I teach two courses, Synaptic Transmission and Plasticity (BIO 1190) and Cellular Physiology and Biophysics (BIO 1100).
|BIOL 1190 - Synaptic Transmission and Plasticity|